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| Name | Class |
|---|---|
| Children's National Research Institute | OTHER |
| Medical College of Wisconsin | OTHER |
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This is a pilot study which will test the safety and feasibility of hypothermia treatment as adjunct therapy to conventional treatment of hyperammonemic encephalopathy (HAE) in neonates versus conventional treatment (dialysis, nutritional therapy, and ammonia scavenging drugs) only. The endpoint of the pilot study will be reached when either 24 patients have been enrolled and no serious adverse events were observed, when no patient has been enrolled in 5 years, or when serious adverse events occur which are clearly linked to the use of hypothermia. These would be serious complications not seen in patients on conventional therapy (dialysis , nutritional therapy, ammonia scavenging drugs) for HAE.
Children with neonatal onset Urea Cycle Disorders or Organic Acidemias develop hyperammonemia (high ammonia levels) and fall into coma often causing brain damage. For these children to be able to benefit maximally from available long-term treatment and solid organ transplant, outcome of the neonatal onset crisis must be improved. Animal experiments and small clinical trials have indicated that hypothermia protects the brain during hyperammonemia. This pilot study investigates whether adjunct hypothermia therapy in addition to standard of care treatment is feasible and safe in babies with high ammonia levels in coma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adjunct Hypothermia Arm | Experimental | Patients that receive adjunct therapeutic hypothermia in addition to standard of care therapy |
|
| Historic Controls | Other | Patients that were treated with standard of care therapy for the same conditions at the sponsoring institution over the past 10 years. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Therapeutic Hypothermia | Other | After obtaining written consent, patients are cooled to 33.5°C (+/- 1°C ) for 72 hours and and then rewarmed by 0.5°C per every 3 hours over 18 hours. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with unexpected Serious Adverse Events as a Measure of Safety and Tolerability | The DSMB meets within 3 weeks of each case, no later than 5 weeks after initiation of hypothermia therapy and assesses the safety and feasibility of adjunct hypothermia treatment in this patient group. The treatment of neonates and very young infants in hyperammonemic coma is very complex and adding hypothermia therapy to this treatment could not be feasible, the pilot study therefore also assesses the feasibility of adding hypothermia therapy to the standard of care treatment. | Participants will be followed for the duration of the hospital stay, an expected average of 5 weeks |
| Feasibility of hypothermia therapy as adjunct therapy to the complex standard of care therapy | The standard of care therapy is very complex. It includes renal replacement therapy, metabolic diet intervention, and ammonia scavenger use. The pilot study will assess primarily for the first 72 hours of treatment and secondarily for the duration of the hospital stay, an expected average of 5 weeks, whether adding hypothermia to this already complex treatment is feasible. | During the first 72h of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Time to normalization of ammonia level | One of the effects of hypothermia treatment is an overall slowing of metabolism which should cause less ammonia to be produced. If this is correct this should lead to a faster normalization of the ammonia level by renal replacement therapy. | During the first 72 hours of treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Uta Lichter-Konecki, MD, PhD | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010 | United States | ||
| Columbia University, Morgan Stanley Children's Hospital |
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| Label | URL |
|---|---|
| National Urea Cycle Disorders Foundation (Family Organisation) | View source |
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|
| Standard of Care Therapy | Other | Patients with hyperammonemia and encephalopathy requiring renal replacement therapy due to a urea cycle disorder or organic acidemia that were treated at Children's National Medical Center over the past 10 years. |
|
|
| New York |
| New York |
| 10027 |
| United States |
| Medical College Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| ID | Term |
|---|---|
| D056806 | Urea Cycle Disorders, Inborn |
| D022124 | Hyperammonemia |
| D053609 | Lethargy |
| D003128 | Coma |
| D001927 | Brain Diseases |
| D012640 | Seizures |
| D001929 | Brain Edema |
| D020163 | Ornithine Carbamoyltransferase Deficiency Disease |
| D020165 | Carbamoyl-Phosphate Synthase I Deficiency Disease |
| D020159 | Citrullinemia |
| D056807 | Argininosuccinic Aciduria |
| D056693 | Propionic Acidemia |
| C537358 | Methylmalonic acidemia |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D014474 | Unconsciousness |
| D003244 | Consciousness Disorders |
| D040181 | Genetic Diseases, X-Linked |
| D028361 | Mitochondrial Diseases |
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| ID | Term |
|---|---|
| D007036 | Hypothermia, Induced |
| D017679 | Cryotherapy |
| D064590 | Cool-Down Exercise |
| D003956 | Dialysis |
| D006435 | Renal Dialysis |
| D000079664 | Continuous Renal Replacement Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D000096063 | Post-Exercise Recovery Techniques |
| D026741 | Physical Therapy Modalities |
| D012046 | Rehabilitation |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D055598 | Chemical Phenomena |
| D017582 | Renal Replacement Therapy |
| D016060 | Sorption Detoxification |
| D005112 | Extracorporeal Circulation |
| D013514 | Surgical Procedures, Operative |
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